The precise sequence and nature of the fundamental biochemical and endocrine response to hypovolemia are unknown. Under ordinary circumstances this makes little difference; unless blood or fluid loss is profound, homeostatic mechanisms effectively maintain life until blood volume is restored. When hypovolemia persists, however, many data from our laboratory and from other investigators clearly indicate that a profound disturbance develops in energy metabolism which in time progresses to tissue and organ disfunction. A concept of irreversible shock is considered only to reflect our ignorance of mechanisms rather than a valid physiological entity. Since the mechanisms responsible for these changes are largely unknown, the primary goal of this continuing study is to determine the biochemical and physiological basis for loss of tolerance to persisting hypovolemia. If a better comprehension of the dynamic sequence of inter-related events that occur during hypovolemia can be developed, it should provide a more rational basis for therapy. The specific aims of this study are: (1) To characterize the biochemical and endocrine alterations that occur during shock. (2) To relate these changes to the hemodynamic function of various organs.